VI. Wittig Reaction, Synthesis of 3-Methylene-4-cholesteneA. Reaction

B. Reaction ProcedureThe Instant Ylid used in this experiment is a mixture of methyl triphenylphosphene

bromide and sodium amide. The reagent bottle should be kept in a refrigerator stored in adesiccator over phosphorous pentoxide. An opened bottle does not maintain its activity verylong. The THF has been dried and may be used directly from the bottle.

Weigh out rapidly 300 mg of the instant Ylid. Do not be concerned about an excess. Ifyou go over this amount, just make a note and use the entire amount Rapidly close thebottle, add the instant Ylid to a 5 mL vial, and close it with a drying tube containing CaCl2.Insert a spin vane, add about 1.0 mL of anhydrous tetrahydrofuran, and commence stirring.The two reagents react to form the yellow Ylid. If the solution does not turn bright yellow,the Instant Ylid is probably bad and a new reaction should be started using fresh material.After about 5 min, add 150 mg (0.39mmoles) of 4-cholesten-3 one. The reaction will be fol-lowed by TLC.

C. This Layer ChromatographyUse alumina TLC plates with fluorescent indicator. The developing solution is 10%

methylene chloride in hexane. The developing chamber is a 400 mL beaker and watch glasswith a sheet of saturated filter paper around the wall. Spotting is done with microcapillariesprepared by drawing out mp tubes in a flame. Spots should be as small as possible. For thestandard, use a sample of the starting material dissolved in methylene chloride. As soon asthe reaction is started, remove a sample and spot it on the TLC plate along with a sample ofthe standard. Develop the TLC plate immediately, mark the position of the solvent front witha pencil, allow the solvent to evaporate, and observe the results under the UV-lamp. Drawcircles around the spots with a pencil. Continue to sample the reaction mixture and run theTLC about every 10 minutes. The starting material and the triphenylphosphene oxide shouldnot move at all, whereas the product should show appreciable migration. The end of thereaction may be determined by the appearance of the TLC plate.

D. Work-up ProcedureA reaction time of 20-30 minutes should be sufficient. The yellow color may change to

a tan, but if there is an excess of Ylid, the color may then change back to yellow. At the endof the reaction add 1.0 mL of 25% NaOH and stir briefly. Add 1 mL of hexane, seal thereaction flask, and shake. Allow the layers to separate and transfer the top hexane layer to a

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centrifuge tube. Repeat this extraction with hexane two more times and combine all theextracts in the centrifuge tube. Wash the hexane extracts a couple of times with saturatedNaCl solution.

Prepare a chromatography column in a long micropipet. After adding a small wad ofcotton, add successively 1 mm of sand, 1.5 cm alumina, 4 cm of magnesium sulfate, and 1mm of sand. Run the hexane solution through this column catching the effluent in a conicalvial. Wash the column with about a mL of hexane and check the purity with TLC. Evapo-rate the solution to dryness. The product will crystallize, but it is probably contaminated withtriphenylphosphene oxide. This must be removed chromatographically on alumina. Dissolvethe solid in about 1.5 mL of hexane and run it through a column of about 4 cm of alumina ina long micropipet, while collecting the effluent in a tared conical vial. Evaporate the hexaneunder a stream of nitrogen with heating and allow the residue to crystallize. Scratching thewalls will induce crystallization. Determine the weight, mp, and IR spectrum (in CC1J.Does the ER spectrum agree with the proposed structure.

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E. Report: The Wittig Reaction

Name Date Exp. No.

Chemical Reaction:

Reagents:

Compound MolWL Density Wt, mg Vol. nL mmole

Products:

Compound MolWL WL, mgTheoretical

mmolTheoretical

Attach IR spectrum

Yield mg.

Yield %

mp or bp range

mmol

., Lit.

I.R. bands and assignments

Evidence for the confirmation of structure

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